HIV is primarily a sexually transmitted disease, and topical microbicides applied intravaginally may be the most realistic short-term approach to stopping the spread of AIDS. The purpose of this project is to use the SIV/rhesus macaque system to determine if the vaginal irritation that occurs from chronic use of virucidal spermicides containing nonoxynol-9 can enhance the vaginal transmission of SIV. The initial studies involved determining which N-9 exposure protocol produces vaginal irritation in rhesus macaques. Four animals were exposed intravaginally to 1 ml of N-9 containing spermicide (Gynol II, Ortho Inc.) twice a day for 28 days. At 1, 24, 48 and 72 hours after the last N-9 exposure, the animals were examined. All the animals were reexamined at 7 days after the last N-9 exposure. Another group of 4 animals were exposed to N-9 spermicide twice a day for 42 days. The cervicovaginal examination of the 28 day exposed animals revealed edema and erythema in the vaginal and ectocervical mucosa but obvious focal ulcers or erosions were not seen grossly. The cervicovaginal examination of the 42 day exposed animals revealed more severe edema and erythema in the vaginal and ectocervical mucosa; and 2 of 4 animals had focal mucosal ulcers or erosions which could be seen grossly. These lesions were multifocal, well demarcated and erythematous. The lesions were particularly prominent in the vaginal fornix and were present at 24 and 48 hours after the N-9 exposure. In the most severely affected animal, the lesions were only partially healed at 7 days post-N-9 exposure. Another group of animals will be similary exposed to N-9 and challenged vaginally with a low dose of SIV to determine if the irritation enhances the vaginal transmission of SIV. *KEY*Vaginal microbicides, HIV transmission, Vaginal irritation